The opioid drug morphine effectively relieves severe pain, but it can also trigger addiction-related processes in the brain. That's why opioid painkillers are strictly controlled in many countries. New research by American scientists on mice suggests that these effects might be separable: pain relief remained, while the brain stopped forming the usual association between morphine and reward, reports infohub.kz.
Morphine and other opioids act not only on pain centers but also on the brain's reward system. Morphine increases dopamine in the nucleus accumbens, a region involved in motivation, learning, and association formation. For a long time, scientists believed that this dopamine increase helps the brain remember the link: taking morphine is associated with pleasure, so it's desirable to repeat. However, the new study shows the mechanism may be more complex.
The researchers examined a small group of cells in the nucleus accumbens—cholinergic interneurons—which release the neurotransmitter acetylcholine. They found that morphine suppresses the activity of these cells and reduces acetylcholine release. The scientists hypothesized that this change might be necessary for forming the association between morphine and the feeling of reward.
To test the hypothesis, the researchers used a technology called DART, which allows targeting specific cell types. With this technology, they modified naloxone—a drug that blocks opioid effects—so that it could prevent morphine's action specifically on cholinergic neurons in the nucleus accumbens, without blocking the drug's effects elsewhere in the brain. After that, mice were given morphine and tested to see if they would return to the place where they received the drug. This test is used to assess whether an animal has formed an association between a specific place and the pleasant effect of a substance.
When morphine's action on cholinergic neurons was blocked: mice stopped developing a preference for the place associated with morphine; the pain-relieving effect of the drug remained; morphine still increased dopamine levels in the nucleus accumbens. So, in mice, a mere increase in dopamine was not enough to form an association with reward. The results point to a more complex mechanism of morphine action. The drug simultaneously increases dopamine and reduces the activity of cholinergic neurons, leading to decreased acetylcholine release. The researchers suggest that it is the combination of these processes that may help the brain form the link between morphine and its pleasant effect.
The authors believe the identified mechanism opens a potentially new target for developing painkillers. Theoretically, scientists could try to create drugs that retain strong pain-relieving effects but are less likely to lead to addiction. Further research will need to confirm whether this approach works not only in mice but also in humans. Earlier this year, scientists tested a new non-opioid drug that does not cause addiction and could potentially replace opioids after surgeries, reported Kursiv.